Esters, coordinated amino acid

There are a few documented examples of studies of ligand effects on hydrolysis reactions. Angelici et al." investigated the effect of a number of multidentate ligands on the copper(II) ion-catalysed hydrolysis of coordinated amino acid esters. The equilibrium constant for binding of the ester and the rate constant for the hydrolysis of the resulting complex both decrease in the presence of ligands. Similar conclusions have been reached by Hay and Morris, who studied the effect of ethylenediamine... 

Hydrolysis of the N-coordinated amino acid ester complexes with 4M HC1 leads to the corresponding complexes containing the N-coordinated amino acid.136... 

The efficacy of coordinated nucleophiles has been established for the intramolecular hydrolysis of numerous substrates for example, coordinated amino acid esters (5), amino nitriles (jj,7)... 

Amino acid esters act as chelates to Co111 for example, the /3-alanine isopropyl ester is known as both a chelate and as an /V-bonded monodentate,983 and the mechanism of hydrolysis of the ester, which is activated by coordination, to yield chelated /3-alanine has been closely examined. 

Typical syntheses of Co(III)-amino acid, amino acid ester, and dipeptide ester chelates are described below. The NMR spectra of the isolated products were in accord with expectation. The procedures given here are generally applicable, except for that given for [Co(en)2((iS)-GluOBzl)]I2. If this method is used to coordinate amino acids that are only partially soluble in Me2SO, more forcing conditions (extended reaction times, 1-5 h, 50-60°C) may be required. Dipeptide ester complexes are not always as amenable as [Co(en)2 (Val-GlyOEt)]I3 to crystallization from water. 

Table 6.3 Effect of Metal Coordination on Rate Constants for Base Hydrolysis of Amino Acid Esters at 25 °C...

Reactions of the ligand which are very slow in the absence of an electron pair acceptor or metallic coordination center. Basic hydrolysis of amino acid esters is an example of such a reaction. 

It has been known for many years that the rate of hydrolysis of a-amino acid esters is enhanced by a variety of metal ions such as copper(II), nickel(II), magnesium(H), manganese(II), cobalt(II) and zinc(II).338 Early studies showed that glycine ester hydrolysis can be promoted by a tridentate copper(II) complex coupled by coordination of the amino group and hydrolysis by external hydroxide ion (Scheme 88).339 Also, bis(salicylaldehyde)copper(II) promotes terminal hydrolysis of the tripeptide glycylglycylglycine (equation 73).340 In this case the iV-terminal dipeptide fragment... 

Essentially three different routes can be considered for the base hydrolysis of an amino acid ester in the presence of a metal ion (equations 8-10). In general terms hydrolysis of the monodentate N-coordinated ester (equation 8) would be expected to be somewhat similar to base hydrolysis... 

Both alkaline proteases form an intermediate, the acyl-enzyme complex, on the reaction coordinate from the amino acid component to the dipeptide, which is formed by the triad Ser-(or Cys-)-His-Asp (or -Glu) (see Chapter 9, Section 9.5). The acyl-enzyme complex can be formed with the help of an activated amino acid component such as an amino acid ester. The complex can react either with water to the undesired hydrolysis product, the free amino acid, or with the amine of the nucleophile, such as an amino acid ester or amide, to the desired dipeptide. The particular advantage of enzyme-catalyzed peptide synthesis rests in the biocatalyst specificity with respect to particular amino acids in electrophile and nucleophile positions. Figure 7.26 illustrates the principle of kinetically and thermodynamically controlled peptide synthesis while Table 7.3 elucidates the specificity of some common proteases. 

Three research groups discovered almost at the same time that non-C2-symmetrical oxazolines of the type 32 can be even more effective ligands for asymmetric catalysis than type 4 ligands (Fig. 11). For the palladium-catalyzed allylic substitutions on 62, record selectivities could be reached using 32 (X = PPhj) [30]. It seems that not only steric but also electronic factors, which cause different donor/acceptor qualities at the coordination centers of the ligand, seem to play a role here [31]. The reaction products can subsequently be converted to interesting molecules, for example 63 (Nu = N-phthalyl) can be oxidized to the amino acid ester 64 [32]. 

Two mechanisms of cobalt(III)-mediated peptide-bond cleavage have been investigated. The first one involves hydrolysis of a directly activated amino acid ester, or peptide (equation 4). The other mechanism involves the intramolecular attack of an amino acid ester or peptide by a cis coordinated hydroxide or water molecule (equation 5). In both cases, the cobalt(III) complex must have two open coordination sites cis to each other. For the directly activated mechanism, these sites are needed to bind the amino acid ester or peptide. The intramolecular reaction requires one site for coordination of the ester or peptide, and one site for the coordination of the hydroxy or water molecnle. One of the initial cobalt(III) complexes to be investigated was... 

When amines are snbstitnted for hydroxide as the base, there is no change in the rate of hydrolysis. This is becanse amines do not catalyze the hydrolysis of amino acid esters instead they prefer to add directly to the carbonyl carbon to form the corresponding amides. In this reaction the rate-limiting step is not the addition of amine, bnt rather the deprotonation of the coordinated amine by another base (eqnation 8). The of the tetrahedral intermediate is approximately 7 since almost any nonsterically hindered base with a pTTa above 7 can deprotonate it. " ... 

The hydrolysis of amino acid esters by directly coordinated hydroxy or water molecules is slower than the corresponding... 

The hydrolysis of peptides by coordinated water or hydroxide follows a path similar to that of amino acid esters (equation 10). The rate of hydrolysis is 10 times faster for coordinated water compared to coordinated hydroxide. As with the hydrolysis of amino acid esters, the attack of the coordinated water or hydroxy group is the rate-limiting step in the hydrolysis of peptides. However, it has been shown that the elimination of the amine group is an important featme in the mechanism. 

Amino acid esters, amides, and peptides can be hydrolyzed in basic solution, and the addition of many different metal ions speeds the reactions. Labile complexes of Cu(II), Co(ll), Ni(II), Mn(II), Ca(II), and Mg(II), as well as other metal ions, promote the reactions. Whether the mechanism is through bidentate coordination of the a-amino group and the carbonyl, or only through the amine, is uncertain, but seems to depend on the... 

Alexander and Busch first described the preparation of complexes of the type cis-[Co(en)2(CH2CHjC02R)Cl]Cl2 (29) by reacting the appropriate amino acid ester hydrochloride with trans-[Co(en)2Cl2]Cl in aqueous solution, the free amino acid ester being generated in situ by the presence of a weakly coordinating base such as McaNH. 

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